Study Links Excess Vitamin A and Birth Defects

By JANE E. BRODY

Published: October 7, 1995

Women who consume excessive amounts of vitamin A during the early months of pregnancy can cause serious birth defects in their unborn children, a large new study has shown.

The babies of women who consumed more than 10,000 international units of vitamin A daily -- nearly four times the recommended amount -- from supplements or food or both were more likely to be born with malformations of the head, heart, brain and spinal cord.

The amounts that place babies at risk are currently found in a single pill in some vitamin preparations and can be readily obtained if more than one vitamin supplement is taken daily. In fact, one of the researchers said he and a colleague recently bought single-nutrient supplements containing 25,000 international units of vitamin A.

Although high doses of vitamin A are known to cause birth defects in laboratory animals and the vitamin's chemical relatives have damaged human infants, the new study is the first to quantify the risk of prenatal vitamin A in a large population and to establish what doses might be harmful. The study showed that 1 baby in 57 born to women taking doses of vitamin A above 10,000 international units daily was damaged as a result.

The higher the doses consumed, the greater the risk, the researchers found. Babies born to women who consumed more than 10,000 international units of the vitamin daily were 2.4 times as likely to be born with such defects as babies exposed to 5,000 international units or less. But babies exposed to 20,000 international units during the first three months of gestation were about four times as likely to be born with defects that included cleft lip, cleft palate, hydrocephalus and major heart malformations.

The study was conducted by Dr. Kenneth J. Rothman, an epidemiologist, and his colleagues at Boston University School of Medicine among 22,748 pregnant women in the Boston area who were identified between October 1984 and June 1987 and questioned in detail about what they ate and what supplements they took. The overwhelming majority of the women studied, 98.6 percent, consumed less than the amount of vitamin A identified as potentially hazardous.

Vitamin A, when taken during pregnancy, is helpful in cell differentiation and is an essential nutrient in a baby's development. But Dr. Rothman said in an interview that national surveys had indicated that 2 percent to 5 percent of women of childbearing age consumed more than 10,000 international units daily.

The findings, which are to be published on Nov. 23 in The New England Journal of Medicine, were released yesterday because of their public health importance. The researchers urged women to avoid taking supplements that exceed 4,000 to 8,000 international units daily, the amount now commonly found in prenatal multivitamins. They made a similar recommendation for women who may become pregnant.

Because vitamin A is stored in the body for long periods, women who take large amounts even during the months before becoming pregnant could place their babies at risk of malformations, the researchers suggested.

In addition to supplements, vitamin A is found in most animal foods, and in especially large amounts in liver. A three-ounce serving of cooked beef liver, for example, may contain more than 30,000 international units of it. Even if women took no supplements, those who frequently consumed liver could exceed safe levels of vitamin A, the researchers said. Other foods containing vitamin A include dairy products, eggs, meats, poultry, fish and fortified foods like certain breakfast cereals.

The researchers pointed out that beta-carotene, which the body can convert into vitamin A, is not associated with an increased risk of birth defects. Dr. Rothman said that women need not be concerned about eating too many vegetables and fruits that are rich in beta-carotene or about taking supplements that contain beta-carotene. The body converts beta-carotene into vitamin A in amounts that do not exceed safe levels.

The Council for Responsible Nutrition, an association of nutritional supplement producers, said that in 1987 it recommended that supplements supply no more than 10,000 international units of vitamin A when sold as a single nutrient and no more than 8,000 international units in prenatal multivitamins. The council also advised that products be labeled to warn women who may become pregnant not to exceed 10,000 international units daily of supplemental vitamin A.

The Boston researchers and the industry council pointed out that since the 1987 recommendation, most multivitamin producers reduced the amounts of vitamin A in each tablet or capsule and that many companies now substituted beta-carotene for vitamin A in some or all of their products.